The proposed work has the long-term objective of elucidating conditions which favor the development of enhancing or "blocking" antibodies (or factors) and characterizing such blocking factors so that they can be reliably detected and quantified in vitro. The specific objectives are: 1) to characterize the immunochemical nature and specificity of enhancing factors in human alloimmune plasmas, using multiparous women as the major source of such factors and cells from their husbands and unrelated donors for absorption experiments to determine specificity, 2) to determine whether serum blocking factors present in cancer patients, pregnant women, and patients accepting allografts are similar, and 3) to study, in a mouse model, conditions favoring the development of enhancing factors and enhancement by exploring the effects of pregnancy, gestational hormones, and sources and maturity of the immunizing tissues, and the mode of presentation of the alloantigens to the host. This knowledge may reveal possible approaches to the control of rejection of organ or tissue grafts and may lead to means of turning off such mechanisms in cancer. BIBLIOGRAPHIC REFERENCES: Schiff, R.I., Mercier, D., and Buckley, R.H.: Effects of gestational hormones on human lymphocyte responses in vitro. Cell. Immunol. 20:69-80, 1975.